Clinical and mutational analysis of 7 children with X-linked adrenal dysplasia congenita / 中华医学遗传学杂志

OBJECTIVE@#To summarize clinical manifestations, inheritance pattern and mutations of NR0B1 gene in 7 children with X-linked adrenal dysplasia congenita (XL-AHC).@*METHODS@#Clinical data of the 7 children was collected. Next-generation sequencing was carried out to detect potential mutations in the coding regions of adrenal gland-related genes. Suspected mutations were verified with Sanger sequencing.@*RESULTS@#In all of the children, the initial symptom was adrenocortical insufficiency. Five cases had neonatal onset, while the remaining two developed it at the age of 2. Three cases (42.9%) had a short stature and 1 showed growth retardation (14.3%). Of the 7 cases, 6 (85.7%) had mutations occurring in exon 1, and 1 (14.3%) had it occurring in exon 2. Four cases (57.1%) were frameshift mutations, 2 cases (28.6%) were nonsense mutations and 1 case (14.3%) was missense mutation. Two mutations were known to be pathogenic, and 5 had not been reported previously. Maternal inheritance was found in 6 cases. Three children had a maternal uncle died of unexplained causes. The mothers of 2 children had a history of spontaneous abortions. One child had a brother died of unexplained reason.@*CONCLUSION@#Male children with primary adrenal insufficiency should be routinely checked for NR0B1 mutations, especially those with a family history. mutations of NR0B1 gene occur mostly in exon 1, with frameshift mutations being the most common type. The development of all patients with XL-AHC should be closely monitored during follow-up.

Clinical features and genetic analysis of seven patients with congenital hyperinsulinism / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze clinical characteristics, genetic mutation and therapeutic effect of seven patients diagnosed with congenital hyperinsulinism(CHI).</p><p><b>METHODS</b>Clinical data for the patients was retrospectively analyzed.</p><p><b>RESULTS</b>All patients presented with hyperinsulinism(serum insulin:2.0-58.4 mU/L),even after hypoglycemia (blood glucose: 0.7-2.39 mmol/L) has developed. Mutations were identified in 4 patients (57.1%), which included a heterozygous c.262C to T(p.R88C) mutation in exon 4 of the UCP2 gene, a heterozygous c.1495C to A(p.G499C) mutation in exon 12 of the GLUD1 gene, a heterozygous c.1493C to T(p.S498L) mutation in exon 1 of the GLUD1 gene, and a heterozygous c.4432G to A(p.G1478R) mutation in exon 37 of the ABCC8 gene. The patient carrying a maternally inherited ABCC8 mutation was treated with cornstarch and had his blood glucose kept normal. All other patients responded well to diazoxide.</p><p><b>CONCLUSION</b>A genetic diagnosis was attained for 51.7% of patients in this study. Mild CHI patients can have their blood glucose controlled by giving cornstarch. Diazoxide is safe and effective for most CHI patients.</p>